Mechanistic overview of ADP-ribosylation reactions

ADP-ribosylation reactions consist of mono-ADP-ribosylation, poly-ADP-ribosylation and cyclic ADP-ribosylation. These reactions play essential roles in many important physiological and pathophysiological events. The types of chemical linkages, the evolutionarily conserved motif within the enzymes to determine the target specificity, stereochemistry of the ADP-ribosylated products, and the chemical reactions taking place among the enzymes and substrates are discussed. •Evolutionarily distinct ARTs contain different motifs at their catalytic cores.•Chemical reactions of poly- and mono-ADP-ribosylations are discussed.•Strained NAD+ plays an important role in ADP-ribosylation reactions.•Most ARTs catalyze ADP-ribosylation with inversion of configuration at the ribose.•Mechanisms for non-transferases mediated ADP-ribosylations are discussed.